Lymphosarcoma is a group of malignant cancers of the lymphoid tissues. Mouse lymphosarcoma cell lines (RAW117 and PU15) closely parallel highly malignant human lymphosarcoma (malignant lymphocytoma) in cell type, disease course, distribution and organ involvement. We will develop malignant variant cell lines of RAW117 and PU15 by sequential in vivo selection methods to obtain stable tumor cell variants of differing malignant potentials and organ preferences in vivo. Preliminary evidence indicates that liver- or spleen-preferring RAW117 variants of high in vivo malignant potential can be selected using these techniques. The surfaces of these variant cell lines will be examined for biochemical, immunological, morphological and enzymatic changes to determine which cell surface characteristics are important in lymphosarcoma malignancy and its neoplastic distribution in vivo. Attempts will be made to use this information to block or modify the extent, location and course of highly malignant lymphosarcoma in syngeneic hosts. In addition, a common problem in lymphosarcoma treatment is acquired resistance to chemotherapy. Sensitivities of these different malignant variants to chemotherapeutic drugs (alkylating agents, hormones and antimetabolites) will be determined and drug-resistant variants selected in vitro and eventually in vivo. The cell surfaces of the drug-resistant lines will be compared with drug-sensitive lines to see if cell surface characteristics are modified when the cells acquire resistance and determine possible differences between resistant and sensitive cell lines of differing in vivo malignant potential.